New Theory on Causes of Atopic Diseases
Various factors such as genetic factors, the pollen, dust mites, chemicals, for example, formaldehydes, and westernized food are regarded as a cause that leads to an atopic disease. However, the accurate cause of the disease is not clear still. As immunological consequences exhibited in atopic diseases, there are unique characteristic that Th1 cells are activated when epidermis is infected, and also Th2 cells are actively active as one of phenomena, which are exhibited at the time of continuously exposing to huge antigens, such as parasitization, or a kind of mechanism for controlling immunomodulary. The present invention has no the emphasis on the unique immunological phenomena exhibited in the atopic diseases. However, in the present invention, it is considered that the phenomenon of permeating blood proteins exuded from blood vessel into skin tissues due to metabolism imbalance or metabolic disorder of body is the start and fundamental cause of an atopic disease. Thus, it is believed that immune reactions generated in atopic diseases are caused by an exudation of blood proteins. Based on the above consideration, the present invention tried to solve the problems. Furthermore, it is also considered that psoriasis is caused by an exudation of blood proteins, and thus the present invention suggests a new therapy for treating psoriasis based on the above cause.
Prior to the 1980's (prior to the 1970's in USA or UK), the frequency of a patient suffered from an atopic disease is not very high, and it has never been a social problem. However, since the late 1980's, the frequency of a patient suffered from an atopic disease has drastically increased, and recently, one of five elementary school students shows symptoms of an atopic disease. Accordingly, an atopic disease became a serious social problem. Comparison between the 1970's and 2000's indicates that air pollution decreases significantly as compared with that of 20 to 30 years ago due to prohibition of use of leaded gasoline, strong government regulation on an automobile exhaust discharge, an introduction of a public transportation using natural gas, a regulation of plant dust, a policy of grouping (making an industrial complex) plants discharging pollutants, and the like. For this reason, it is believed that the patients suffered from an atopic disease are not increased by the current environment and conditions.
The current living space has a much larger window than that in the housing of the 1970's, and the structure is changed such that the indoor of the housing receives much more light of the sun. A vacuum cleaner with a micro-filter is becoming more and more common, a washing machine with a bactericidal function is used, and detergents are getting stronger and are diversified. Dust mites are difficult to live in the current conditions than in previous years. That is, it is difficult to explain the relationship between the frequency of atopic diseases occurrence and dust mites. There are various grasses in a rural area as compared with the city. The concentration of pollen is far higher in a rural area as compared with the city. However, the frequency of atopic disease occurrence in the city is higher than that in a rural area. There is no relationship between the concentration of pollen and the frequency of atopic disease occurrence. Thus, it is difficult to consider pollen as a cause of atopic disease.
The things that are conspicuously changed in the city culture as compared with the 1970's includes a caterer's shop, various fast-food restaurants, a convenient public transportation system, a private car, and the like. Furthermore, since the mid-1980's, the most notable change is a change of food, and specifically, cooking oils (soybean oils, corn oils, olive oils, grape seed oils, cottonseed oils, and the like) and the like are supplied in bulk at a low cost. Thus, food heated in oil using these oils become popular unexpectedly. Additionally, margarine containing a large quantity of trans-oil and linoleic acid becomes popular. In accordance with the advertisement that margarine lowers a level of cholesterol and thus is good for one's health, margarine consumption had sharply increased for a while. Actually, most commercialized vegetable oil products are produced by an extraction process using solvent (for example, n-hexane). As a result, the most commercialized vegetable oil products are pure neutral lipids in a very clear and transparent state with no polar lipids, containing a great quantity of unsaturated fatty acid. In terms of an evolutionary process of human, it can be easily inferred that people take currently in too much vegetable neutral lipids having a great quantity of unsaturated fatty acid. That is, it is believed that there is a physiologically revolutionary change that can greatly affect a lipid metabolism of human. From a long evolution, human has eaten fatty acid containing cis-type fatty acid in natural state, but now a great quantity of trans-type fatty acid. As a result of evolution, human body does not have enzyme capable of converting trans-type fatty acid into cis-type fatty acid. An ingestion of trans-type fatty acid allows the whole lipid metabolism to slow down. Due to developments of public transportation and convenience, the physical activity level is rapidly decreased, and thereby the condition incapable of converting the ingested fatty acid into energy in a human body is formed. In addition, it may be considered that a living temperature accepted by a human body is sharply increased due to developments of heating system and clothing materials.
In conclude, it may be considered that the conditions have been made to be good for generating skin diseases such as an atopic disease and psoriasis since the imbalance of lipid metabolism is caused due to a decrease of the conversion of lipids into energy, overindulgence of neutral lipids containing unsaturated fatty acid, an intake of trans-oil, and a decrease of physical activity level, and the environment that can make an extension of capillary and uncompleted function of capillary is made due to an increase of living temperature.
Differences and Similarities Between Psoriasis and Atopic Disease
A defunctionalization of lung because of ingesting a great quantity of vegetable unsaturated fatty acid can be definitely known from a result of researching by Wolfe et al. (Wolfe R. R., Martini W. Z., Irtun O., Hawkins H. K., Barrow R. E. (2002) Dietary fat composition alters pulmonary function in pigs. Nutrition. 18:647-653). A compliance of lung tissue is lost, and blood plasma proteins are exuded by ingesting vegetable oils thereby affecting the functions. Similarly, skin may be affected by ingesting a great quantity of unsaturated fatty acid. The patients suffered from an atopic disease have high level of HDL-cholesterol (Schafer T., et al., (2003) Intake of unsaturated fatty acids and HDL cholesterol levels are associated with manifestations of atopy in adults. Clin. Exp. Allergy. 33:1360-1367). It can be interpreted that after ingesting lipid, active lipids are delivered to each organs. A delivery of lipids containing unsaturated fatty acid to skin may affect membrane components of epidermal cells and vascular cells, and the unsaturated fatty acids having high fluidity may reduce functions of blood vessel, thereby causing an exudation of blood plasma proteins, particularly albumin and immunoglobulin G (IgG). Such an exudation is accomplished through a gap between blood vessel cells, and as its evidence, sizes of proteins thus exuded are limited. IgG having a size of 150 KDa is easily exuded, but the proteins having larger size than that of the IgG described above are not easily exuded. Such an exudation mechanism can be exhibited in a patient suffered from psoriasis as well as a patient suffered from an atopic disease. It may be deduced that erythroderma or edema exhibited in psoriasis and an atopic disease may occur by generating a change of function or structure of blood vessel except for the case by infection or strong physical stimulation. It is important that psoriasis and atopic diseases are greatly different metabolically. Although the patients suffered from an atopic disease have high level of HDL-cholesterol, the patients suffered from psoriasis have very high levels of blood cholesterol and triacylglycerol. Interestingly, a size of sebaceous gland secreting the production of sebum of neutral lipid components in the patients suffered from psoriasis is too small. According to a simple analysis, it is shown that there may be a problem with the supply of lipids required for synthesizing sebum from blood vessel. A similar case for an atopic disease is that ceramide lipid required for protecting skin is low in epidermis. Although the profiles of lipids contained in the blood of psoriasis and atopic disease are different, an active lipid metabolism in the body is common ground between them. The common ground that is especially worth of notice in the psoriasis and atopic disease is an exudation of blood protein generated in both of the diseases. It can be deduced that although lipid metabolism is actively generated in the body, there may be a problem with a process of delivering lipids to epidermis, or special lipids that are necessarily required are not delivered to epidermis.
New Understanding on Inflammatory Response and Exudation of Blood Protein
The common ground between psoriasis and an atopic disease is that blood proteins are leaked from micro vascular and then exuded to a skin tissue. The exuded proteins have a limited molecular weight, and a large percentage of immunoglobulin G (IgG, 150 KDa) and serum albumin (66 KDa) is contained. It may be expected that the proteins exuded to skin may be slowly dried, bound randomly (random binding with low-affinity), non-specifically bound not selectively bound, or aggregated with each other while increasing an around salt concentration, not like the proteins inside the blood vessel. It may be deduced to continuously generate a vicious circle such that an exuded amount greatly increases by promoting a secretion of histamine due to a physical stimulation through scratching and generating uredo while drying the proteins. It may be deduced that since although there are no allergens or infection invaded from the outside, the phenomenon of non-specific or random aggregation of exuded antibodies can be recognized as a similar signal in the case of the infection, first neutrophils are moved to a tissue, and thus various immune cells may be recruited. Especially, it is illustrated that the phenomenon of recruiting macrophages in a tissue in the cases of chronic atopic diseases is generated by an immunological mechanism of Th2 cells due to a continuous antigen exposure. However, it can be illustrated that such the phenomenon is simply generated by a mechanism for cleaning the aggregation of exuded blood proteins. An example of such a cleaning mechanism includes a clear-up of agglomerated clots of surfactant proteins and lipids by macrophages in an idiopathic alveolar proteinosis. It is possible to explain the movement and activation of eosinophil observed in an atopic disease with regard to a protein exudation symptom. It is well known that eosinophil secretes cationic proteins. It may be one of a simple cytological mechanism for removing the exuded proteins after agglomerating the exuded proteins. Furthermore, it may be simply understood that eosinophil may be recruited in a region of exudation in order to reduce a blood protein exudation that is continuously generated in an atopic disease, like a recruitment of eosinophil in order to control or reduce a blood protein exudation after recruiting eosinophil by infection or sensitization of allergen in pleural cavity.
New Method for Solving Psoriasis and Atopic Disease
Based on the basis suggested above, if the psoriasis and atopic diseases are commonly generated by an imbalance and abnormal of lipid metabolism, and as a result, various inflammatory responses are induced by leaking and then agglomerating the blood proteins leaked from blood vessel in a tissue, a new method for treating the above diseases may be suggested.
As a method for treating the diseases that are most important and preceded, an ingestion of vegetable oils, especially vegetable neutral oils should be suppressed, and food that are cooked by not using a method of producing trans-oils in a cooking process or food containing trans-oils should be ingested. Since such a diet control method should be carried out until lipid components in the body are changed in a certain level, the method requires a considerable amount of time and energy. There are problems that since the patients with an atopic disease suffer from a severe itching, a period for treating the disease is long, but a diet control method must be used.
A second method is a method for alleviating inflammation and then recovering epidermis in a normal state by suppressing a blood protein exudation locally in a diseased area. Such a method is the method previously suggested by the present inventors that is registered as a patient in Australia, Singapore, and Russia in addition to Korea now (Korean Patent No. 0891595, Australia Patent No. 2006217261, PCT Patent No. PCT/KR2006/000638). The method is that the lipid metabolism in relevant cells and vascular cells is changed and an exudation of blood proteins is suppressed by applying the composition including disaturated phospholipids that are present in a great quantity in lung of animal to the diseased area. Such the method requires a treatment period, i.e., 8 to 12 weeks averagely, and in the case of the patient with severe symptoms, it is required for longer periods of time.
A third method is a method suggested in the present patient, and for removing exuded proteins permeated into a diseased area by using a patch for absorbing proteins. It is a method that a most rapid treatment period may be expected, i.e., averagely 10 days, and it is a very stable method since it is not a way for delivering any materials or effective components to skin and quickly alleviates the pain generated by a itching. However, there is the potential for the symptom to reoccur since the proteins may be re-exuded if the method is used without decreasing or suppressing the exudation of blood proteins. A non-recurrent and complete treatment can be expected for a short period of time by simultaneously applying a patch for removing an exudate of blood proteins suggested in the present patient in conjunction with a treatment for suppressing a protein exudation using various ways.